Mirdametinib + BGB-3245 in Advanced Solid Tumors

SpringWorks Therapeutics

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Advanced Solid Tumor

Treatments: Drug: Mirdametinib; Drug: BGB-3245

Study type: Interventional

Funder types: Industry

Identifiers

NCT05580770

MEKRAF-AST-101

Details and patient eligibility

About

A Phase 1/2a open-label, multicenter, dose escalation and expansion study of mirdametinib in combination with BGB-3245 in adult participants with histologically confirmed, advanced (American Joint Committee on Cancer (AJCC) Stage III or IV) metastatic or unresectable solid cancer that is refractory to or has progressed during or after at least 1 line of appropriate prior systemic anti-cancer therapy including chemotherapy, immunotherapy, or appropriate targeted therapy, or for which there is no treatment available, or prior standard of care therapy was not tolerated.

Enrollment: 23 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Able to provide informed consent

• At least 18 years of age on day of signing ICF

• Advanced, metastatic or unresectable solid cancer that has not responded to or progressed during or after at least 1 line of appropriate therapy or for which there is no treatment available or prior therapy was not tolerated.

• Part 1: oncogenic mutation or other genomic aberration of the MAPK pathway

• Part 2: oncogenic mutation or genomic aberration defined below:

  • Cohort A: cutaneous melanoma harboring NRAS mutations.
  • Cohort B: non-small cell lung cancer (NSCLC) harboring a KRAS mutation.
  • Cohort C: NSCLC or cutaneous melanoma harboring BRAF Class II or Class III mutations or BRAF Fusion mutation.

• Must have archival tumor tissue or agree to a fresh tumor biopsy at screening

• Measurable disease per RECIST 1.1

• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2

• Adequate organ function and no transfusion within 14 days of first dose

Key Exclusion Criteria:

• Central Nervous System metastases, leptomeningeal carcinomatosis or untreated spinal cord compression
• History of glaucoma
• Active parathyroid disorder or history of malignancy associated hypercalcemia
• Clinically significant cardiac disease within the past 6 months of signing ICF
• History of toxicity from another RAF, MEK, ERK inhibitor requiring discontinuation of treatment from these agents
• Severe or uncontrolled systemic disease
• Inability to swallow oral medications
• Clinically significant active infection (HIV, Hepatitis B or Hepatitis C)
• History of or ongoing Immune Thrombocytopenia (ITP), Von Willebrand disease and/or other past or present bleeding disorders
• Underlying medical conditions in investigator's opinion to be unfavorable to be a part of the study
• Major surgical procedure or significant traumatic injury within 4 weeks prior to first dose or anticipates need for major surgery while on study
• Systemic anti-cancer therapy within 2 weeks or 5 half-lives before first dose
• Concomitant systemic or glucocorticoid therapy within 2 weeks before first dose
• Concomitant medicines that are strong CYP3A4 inhibitors or inducers within 2 weeks or 5 half-lives before first dose
• Live vaccine within 4 weeks before first dose

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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23 participants in 4 patient groups

Phase 1 Dose Escalation Cohorts Ranging in Dose

Experimental group

Description:

Participants with an oncogenic mutation or other genomic aberration of the MAPK pathway

Treatment:

Drug: BGB-3245

Drug: Mirdametinib

Phase 2 Dose Expansion A

Experimental group

Description:

Participants with cutaneous melanoma harboring NRAS mutations

Treatment:

Drug: BGB-3245

Drug: Mirdametinib

Phase 2 Dose Expansion B

Experimental group

Description:

Participants with NSCLC harboring KRAS mutations

Treatment:

Drug: BGB-3245

Drug: Mirdametinib

Phase 2 Dose Expansion C

Experimental group

Description:

Participants with NSCLC or cutaneous melanoma harboring BRAF Class II or Class III mutation or BRAF Fusion mutation

Treatment:

Drug: BGB-3245

Drug: Mirdametinib